A systematic review of commercial high concentration antibody drug products approved in the US: formulation composition, dosage form design and primary packaging considerations
Three critical aspects that define high concentration antibody products (HCAPs) are as follows: 1) formulation composition, 2) dosage form, and 3) primary packaging configuration. HCAPs have become successful in the therapeutic sector due to their unique advantage of allowing subcutaneous self-administration. Technical challenges, such as physical and chemical instability, viscosity, delivery volume limitations, and product immunogenicity, can hinder successful development and commercialization of HCAPs. Such challenges can be overcome by robust formulation and process development strategies, as well as rational selection of excipients and packaging components.
We compiled and analyzed data from US Food and Drug Administration-approved and marketed HCAPs that are ≥100 mg/mL to identify trends in formulation composition and quality target product profile. This review presents our findings and discusses novel formulation and processing technologies that enable the development of improved HCAPs at ≥200 mg/mL. The observed trends can be used as a guide for further advancements in the development of HCAPs as more complex antibody-based modalities enter biologics product development.
Table 1. List of excipients generally used in protein formulations and their functions
| Excipients | Function | Examples |
|---|---|---|
| Buffer | Maintain stable pH environment | Histidine, Phosphate, Acetate, Citrate, etc. |
| Sugar and polyol stabilizers | Conformational stabilizer for the antibody | Disaccharides – Sucrose, Trehalose, Maltose. Polyols – Sorbitol, Mannitol |
| Tonicity Agent | Maintain iso-tonicity | Sucrose, NaCl, Trehalose, Mannitol |
| Surfactant | Reduce interfacial stress | Polysorbate 20 and 80, Poloxamer 188 |
| Amino acid stabilizers | Stabilize the antibody by buffering or charge interactions or blocking hydrophobic interactions | Arginine, Proline, Glycine, Histidine, Methionine |
| Chelating agent | Prevent metal induced degradation | DTPA, EDTA |
| Viscosity Modifiers | Reduce solution viscosity | Arginine, Proline, Glycine, NaCl |
| Antioxidants | Inhibit oxidation | Methionine |
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Indrajit Ghosh, Hiten Gutka, Mary E. Krause, Ryan Clemens & Ramesh S. Kashi, A systematic review of commercial high concentration antibody drug products approved in the US: formulation composition, dosage form design and primary packaging considerations, Article: 2205540 | Received 11 Oct 2022, Accepted 18 Apr 2023, Published online: 27 May 2023, Download citation https://doi.org/10.1080/19420862.2023.2205540
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